Antibiotic-resistant strains of bacteria present signifcant challenges for treating patients with infectious diseases and conditions. For example, some antibiotics, e.g., fluoroquinolones, are losing their effectiveness due to bacterial resistance, and some antibiotics are not effective against Gram-negative bacteria. These challenges have in some cases worsened since the pace of development for new antibiotics has been slow.
Research directed to the development of new antibiotics, to which bacteria are not resistant, is critically important. N-Benzyl-3-sulfonamidopyrrolidines have been identified as useful small molecule antibiotics and have been shown to inhibit bacterial growth, specifically the growth of Escherichia coli (See Mukherjee, S., et al., Bioorg. Med. Chem. Lett. 17, (2007) 6651-6655). Certain of these small molecule inhibitors have also been identified as inhibitors of the bacterial DNA gyrase enzyme (See Foss, M. H., et al., ACS Med. Chem. Lett., 2011, 2, 289-292). The gyrase enzyme is required for bacterial survival, and thus compounds which inhibit this enzyme represent a new class of antibiotics.
There currently exists a need in the relevant field for new small molecules, such as benzyl-sulfonamidopyrrolidines, which are useful as antibiotics. In particular, there are needs for antibiotics which are useful for killing Gram-negative bacteria and bacteria which are resistant to antibiotics, e.g., vancomycin-resistant bacteria. There also exists a need for new methods for making these small molecules benzyl-sulfonamidopyrrolidines. The present invention meets these needs, as well as others, and provides, inter alia, methods of making and using new small molecule benzyl-sulfonamidopyrrolidines.